A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM)

Phase 1

Terminated

• Conditions: Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Multiple Myeloma
• Interventions: Drug: GS-9219

• Registration Number: NCT00499239
• Lead Sponsor: Gilead Sciences

Brief Summary

Multi-center, open-label, single-dose, dose-escalating Phase I/II study of GS 9219 in adult patients with relapsed or refractory CLL, NHL or MM. Patients will be enrolled into the study in sequential dose cohorts.

Patients will be administered a single IV infusion of GS 9219 on Day 1 of a 21 day cycle and may receive a total of six treatment cycles based on toxicities and response. Patients who demonstrate disease progression will be discontinued from the study. Patients who, at the completion of six treatment cycles, tolerate treatment and show evidence of disease control (response or stabilization) will be eligible to continue receiving treatment at the same dose.

Detailed Description

The primary objective of this study is as follows:

To assess the safety, toxicity, and maximum tolerated dose (MTD) of GS 9219 administered via IV administration once every three weeks (21 days) for six treatment cycles, i.e. for a total of 18 weeks, in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM).

The secondary objectives of this study are as follows:

To determine the pharmacokinetic parameters of GS 9219 for this regimen and patient population.

To assess the antitumor activity of GS 9219 based on Response Rate and Duration of Response. Progression-free Survival and Overall Survival will be assessed if applicable.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-07-09
• Study First Submitted QC: 2007-07-10
• Study First Posted: 2007-07-11
• Primary Completion: 2010-07
• Study Completion: 2010-10
• Status Verified: 2014-01
• Disposition First Submitted: 2014-01-03
• Disposition First Submitted QC: 2014-01-03
• Last Update Submitted: 2014-01-03
• Disposition First Posted: 2014-02-04
• Last Update Posted: 2014-02-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Relapsed or refractory CLL, NHL or MM
• ECOG Performance Status of 0, 1, or 2
• Adequate organ function (protocol defined)
• ECG without evidence of clinically significant ventricular arrhythmias

Exclusion Criteria

• AIDS-related lymphoma
• Subjects with NHL who present exclusively with non-measurable lesions
• Subjects with MM who have non-secretory and/or non-measurable disease
• Recent anticancer therapy (chemotherapy, radiotherapy, and/or biotherapy)within four weeks prior to starting treatment
• Evidence of pulmonary fibrosis
• Other concurrent malignancy
• Uncontrolled concurrent illness
• Receiving chronic, systemically administered steroids
• Known hypersensitivity to nucleoside analogues

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GS-9219	GS-9219	Escalating doses of GS-9219 (5, 8, 11.5, 16, 22.5, 31.5, 44, and 61.5 mg/m\^2) until determination of the maximum tolerated dose (MTD)

Primary Outcome Measures

Name	Time	Method
Determination of MTD	All visits	Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE). The MTD will be the highest dose level immediately below the dose level where two or more of three to six patients experience a dose-limiting toxicity (DLT).

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of GS-9219 and its metabolites	AAA) CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6	Pharmacokinetics (Cmax, Tmax, Clast, Tlast, λz, t1/2, AUClast, AUCinf, and %AUCexp) measured by blood sampling
Response rate	CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6	Response rate measured by: * CLL: National Cancer Institute Working Group (NCIWG) criteria; * NHL - National Cancer Institute (NCI) criteria; Response Evaluation in; * MM - International Myeloma Working Group (IMWG) criteria.
Duration of response	CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6	Duration of response measured by: * CLL: National Cancer Institute Working Group (NCIWG) criteria; * NHL - National Cancer Institute (NCI) criteria; Response Evaluation in; * MM - International Myeloma Working Group (IMWG) criteria.

Trial Locations

Locations (20)

UCSF; 🇺🇸 San Francisco, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Nevada Cancer Institute; 🇺🇸 Las Vegas, Nevada, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Fakultni nemocnice Brno - Bohunice; 🇨🇿 Brno, Czech Republic

Fakultni nemocnice Hradec Kralove; 🇨🇿 Hradec Kralove, Czech Republic

Fakultni nemocnice Olomouc; 🇨🇿 Olomouc, Czech Republic

Fakultni nemocnice Kralovske Vinohrady; 🇨🇿 Praha, Czech Republic

Vseobecna fakultni nemocnice; 🇨🇿 Praha, Czech Republic

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